The response of spleen cells to the T cell mitogen PHA-P was studied in experimentally induced chronic uremia in the rat. The reactivity of spleen cells from chronic uremic rats to mitogens was 2-to 6-fold lower than the response of control spleen cells. We have shown that the response of uremic T and B cells to mitogens can be enhanced by the elimination of a subpopulation of spleen cells that adheres to glass or rayon wool. The characteristics of the adherent suppressor cell in uremic rats were examined. We found that: 1) adherent spleen cells from uremic rats display a more potent suppressor activity than do control adherent cells; 2) the suppression that is mediated by uremic adherent spleen cells cannot be eliminated by pretreatment with indomethacin, while the suppression that is mediated by naturally present adherent cells in the control rat is reversed by pretreatment with indomethacin; 3) the uremic adherent suppressor cell does not have Ia antigens that can be detected by anti-Ia monoclonal antibodies, while control adherent cells have Ia antigens on their surfaces; and 4) both the control and uremic suppressor cells are insensitive to Mitomycin C and do not have any detectable levels of Thy 1 antigens on their surfaces. It appears that immune suppression in uremic rats is mediated by an adherent cell that differs from adherent cells present in control animals.